Eplerenone

Eplerenone

Systematic (IUPAC) name
pregn-4-ene-7,21-dicarboxylic acid, 9,11-epoxy-17-hydroxy-3-oxo, γ-lactone, methyl ester (7α, 11α, 17α)
Clinical data
Trade names	Inspra
AHFS/Drugs.com	monograph
MedlinePlus	a603004
Pregnancy cat.	B3 (Aust)
Legal status	Schedule 4 (Aust), Rx only (US)
Routes	oral
Pharmacokinetic data
Bioavailability	69%
Metabolism	hepatic (CYP3A4)
Half-life	6-8 hours
Excretion	67% renal 32% biliary
Identifiers
CAS number	107724-20-9 Y
ATC code	C03DA04
PubChem	CID 5282131
IUPHAR ligand	2876
DrugBank	DB00700
ChemSpider	10203511 Y
UNII	6995V82D0B Y
KEGG	D01115 Y
ChEBI	CHEBI:31547 Y
ChEMBL	CHEMBL1095097 Y
Chemical data
Formula	C24H30O6
Mol. mass	414.49
SMILES COC(=O)[C@@H]4C\C1=C\C(=O)CC[C@]1(C)[C@@]65O[C@@H]6C[C@@]3(C)[C@@H](CC[C@]23CCC(=O)O2)[C@H]45
InChI InChI=1S/C24H30O6/c1-21-7-4-14(25)10-13(21)11-15(20(27)28-3)19-16-5-8-23(9-6-18(26)30-23)22(16,2)12-17-24(19,21)29-17/h10,15-17,19H,4-9,11-12H2,1-3H3/t15-,16+,17-,19+,21+,22+,23-,24-/m1/s1 Y Key:JUKPWJGBANNWMW-VWBFHTRKSA-N Y
Y (what is this?)  (verify)

Eplerenone (INN) /ɛpˈlɛrənoʊn/ is an aldosterone antagonist used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone, though it is much more selective for the mineralocorticoid receptor in comparison (i.e., does not possess any antiandrogen, progestogen, or estrogenic effects), and is specifically marketed for reducing cardiovascular risk in patients following myocardial infarction. It is marketed by Pfizer under the trade name Inspra. Eplerenone is a potassium-sparing diuretic, meaning that it helps the body get rid of water but still keep potassium.

Medical use

Eplerenone is specifically indicated for the reduction of risk of cardiovascular death in people with heart failure and left ventricular dysfunction within 3–14 days of an acute myocardial infarction, in combination with standard therapies and as treatment against hypertension. It appears equivalent to spironolactone but is much more expensive.^[1]

Adverse effects

Common adverse drug reactions (ADRs) associated with the use of eplerenone include: hyperkalaemia, hypotension, dizziness, altered renal function, and increased creatinine concentration.^[2] Eplerenone may have a lower incidence of sexual side effects such as feminization, gynecomastia, impotence, low sex drive and reduction of size of male genitalia.^[3] Due to the high risk of elevated potassium levels in individuals taking eplerenone, the United States FDA suggests routine checks on the individual's potassium level to screen for hyperkalemia.

Contraindications

Eplerenone is contraindicated in patients with hyperkalaemia, severe renal impairment (creatinine Cl less than 30 ml/min), or severe hepatic impairment (Child-Pugh score C). The manufacturer of eplerenone also contraindicates ( relative C.I. ) concomitant treatment with ketoconazole, itraconazole or other potassium-sparing diuretics (though the manufacturer still considers taking these drugs to be absolute C.I.) Potential benefits should be weighted against possible risks.

Drug interactions

Eplerenone is primarily metabolised by the cytochrome P450 enzyme CYP3A4. Thus the potential exists for adverse drug interactions with other drugs that induce or inhibit CYP3A4. Specifically, the concomitant use of the CYP3A4 potent inhibitors ketoconazole and itraconazole is contraindicated. Other CYP3A4 inhibitors including erythromycin, saquinavir, and verapamil should be used with caution. Other drugs that increase potassium concentrations may increase the risk of hyperkalaemia associated with eplerenone therapy, including salt substitutes,^[4] potassium supplements and other potassium-sparing diuretics.

Lab Synthesis

Steroidal, Aldosterone Antagonists: Increased selectivity of 9α,11-epoxy derivatives. doi:10.1002/hlca.19970800220. 

See also

• Spironolactone
• Aldosterone antagonist
• Canrenone

References